DESCRIPTION (Verbatim from the Applicant's Abstract): The goal of this proposal is to complete the development of a compact, very high performance positron emission tomography (PET) scanner, designed for functional imaging of small laboratory animals. The system, microPET II, will have 1.2 mm spatial resolution in all dimensions and an absolute sensitivity of approximately 500 cps/microCi. This corresponds to a factor of 4 improvement in volumetric resolution and a factor of 2.5 improvement in sensitivity over our initial prototype. The microPET II gantry will measure just 50 x 50 x 12 cm, allowing the system to be located in any research laboratory. The imaging field of view will be sufficient for imaging the major organs (for example heart and brain) and localized tumors in mice and rats. A computer controlled bed will be interfaced to the system to permit dynamic whole-body studies in mice and rats. All the necessary software to control list mode data acquisition, system calibration, quality control, data correction and 3D image reconstruction will developed, along with a user interface. A number of projects related to the use of this new scanner are proposed. The reproducibility and accuracy of radiotracer concentrations determined by microPET II in phantom studies and in vivo will be assessed. Issues related to rapid attenuation correction, placing particular emphasis on the choice of transmission source geometry, will be studied. The necessary hardware and software to permit cardiac gating in the mouse and rat will be developed. Rapid dynamic imaging of the left ventricular blood pool as a means for determining the input function non- invasively in small animals will be investigated. The feasibility of performing motion correction to permit brain studies in conscious animals will be assessed. Finally, the impact of physical limitations (positron range, non-colinearity, spatial distribution of energy deposition in small detectors) on the performance of this scanner will be examined in detail. In addition, basic detector research will continue to seek new approaches to improve the performance (spatial resolution, sensitivity, count-rate performance, energy resolution) and reduce the cost of dedicated animal PET systems. MicroPET II will be a powerful new tool for researchers interested in non-invasive imaging of biological processes in vivo. The performance of this system, particularly its ability to perform detailed PET studies in the mouse, will open up new applications across a broad range of scientific disciplines, including oncology, neuroscience, cardiology, molecular biology, genetics and pharmacology.